The Cryptococcus neoformans capsule: a sword and a shield

Abstract

The human fungal pathogen Cryptococcus neoformans is characterized by its ability to induce a distinct polysaccharide capsule in response to a number of host-specific environmental stimuli. The induction of capsule is a complex biological process encompassing regulation at multiple steps, including the biosynthesis, transport, and maintenance of the polysaccharide at the cell surface. By precisely regulating the composition of its cell surface and secreted polysaccharides, C. neoformans has developed intricate ways to establish chronic infection and dormancy in the human host. The plasticity of the capsule structure in response to various host conditions also underscores the complex relationship between host and parasite. Much of this precise regulation of capsule is achieved through the transcriptional responses of multiple conserved signaling pathways that have been coopted to regulate this C. neoformans-specific virulence-associated phenotype. This review focuses on specific host stimuli that trigger the activation of the signal transduction cascades and on the downstream transcriptional responses that are required for robust encapsulation around the cell.

Fig 1

Different inducing conditions result in various degrees of encapsulation in the wild-type strain. Cells were incubated for 48 h in the specified media. Capsule was visualized by counterstaining with India ink. SC, synthetic complete medium; FBS, fetal bovine serum; Sab, Sabouraud medium.

Fig 2

C. neoformans signal transduction networks that respond to iron, glucose, physiological CO₂, and host pH signals. The dashed lines indicate connections that are established primarily by transcriptional data or homology; these processes require further study to determine the nature of the interaction.

Fig 3

Elements of MAPK cascades in C. neoformans and their roles in capsule regulation.

Fig 4

Signal transduction cascades that regulate titan cell formation. Although some elements of the Pka1 cascade have not been tested explicitly for titan cell formation, the involvement of multiple proteins from this pathway in titan cell formation demonstrates the importance of cAMP/PKA signaling in regulating this phenotype.